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Lab test update - eGFR

Clinical biochemist and GP Dr Berenice Lopez uses a primary care case history to discuss the use of the estimated glomerular filtration rate

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How accurate is eGFR and how much does it vary with age?

The MDRD equation includes the variables age, sex and race in addition to serum creatinine as surrogate for muscle mass to overcome the limitations of using serum creatinine alone. It is one of the few to have been validated against a gold-standard technique for measuring eGFR as well as clinical outcome data. But still, significant error is possible. The MDRD makes certain assumptions, which may not be true:

• Creatinine levels are stable over days or longer. This means that situations where serum creatinine is changing rapidly, such as acute kidney injury, cannot be interpreted.

• Glomerular filtration and muscle mass are the only factors affecting the concentration of creatinine in serum. Creatinine concentrations may also be affected by diet, hydration status, diurnal variation and time to centrifugation.

• Creatinine measurement is accurate. Creatinine values depend on the laboratory method or analyser used. Local method adjustment factors correct for differences, so the MDRD result calculated, say, from the Renal Association website, will not be the same as the local lab result.

• The MDRD equation is valid in all populations at risk. The equation was derived from a large middle-aged population of patients of both white and African-Americans with known CKD and has not been validated in other patient groups. Importantly, the MDRD formula tends to underestimate true GFR at higher levels. It is not valid in pregnant women or children. It is also inaccurate in those with non-standard morphology, such as the malnourished or grossly overweight.

There is debate about the effect of age on eGFR, which may fall by up to 10ml/min per decade after age 40 so that at the age of 80, normal GFR is 60ml/min. The MDRD equation may also underestimate kidney function in over 75s so that in the absence of other abnormalities, an eGFR of 45-60 may not reflect true kidney disease. But current thinking is that interpretation of GFR should not usually be affected by age.

How soon should eGFR be repeated when an abnormally low value is found for the first time?

If a patient is newly discovered to have a low eGFR, they should not be labelled as having CKD unless we know that it is a stable value, present for at least three months.

The first priority is to find out if renal function is deteriorating and how fast.

As there are no previous results to go by, assume that there may have been an acute deterioration and look for precipitating causes. Top of the list of concerns is whether his renal function has become acutely compromised because of dehydration, use of a vasoconstrictor agent such as an NSAID or because his blood pressure has become too low to perfuse his kidneys adequately.

A not uncommon scenario is the patient who becomes dehydrated because they feel too unwell to eat or drink. Patients on ACE inhibitors or ARBs are not able to compensate by the usual mechanisms.

Consider stopping his ACE inhibitor if any of these factors are present until corrected. Generally, low eGFR values should be repeated within two weeks. But big changes in renal function, worrying potassium levels or a sick patient should prompt a repeat test within 24 hours.

On retesting, try to ensure the eGFR is calculated under ‘ideal conditions'. The person should preferably have not eaten a heavy protein load in the previous 12 hours and blood samples should be received and processed by the lab within 12 hours of venepuncture.

If a repeat eGFR confirms the low value, what further assessment should be made?

41211352If, on retesting, the change in eGFR is less than 5%, renal function is probably stable. But if eGFR has declined by more than 5%, renal function is probably continuing to deteriorate and the patient should be monitored.

To clarify the trend, aim to obtain at least three measurements over three months. Note that an overall decline in eGFR of greater than 5ml/min within12 months indicates progressive kidney disease and should prompt referral.

In a patient with stable but reduced eGFR, assess the risk of progression to ESRD. Proteinuria is the best indicator of this risk so check that you have sent an ACR (or PCR) on an early morning urine sample to the laboratory. Check also for haematuria.

Optimise blood pressure control as well as other CV risk factors. Fasting blood glucose and lipids may be helpful. Consider adding low-dose aspirin or a statin. Arrange a renal ultrasound if indicated.

The difficulty GPs face is balancing what may be best for their elderly patients with what national guidelines and the QOF are requesting them to do, particularly when exception reporting is so closely scrutinised. ACR testing and the potential initiation or up-titration of ACE inhibitors in elderly patients with other comorbidities may not always be appropriate.

ACE inhibitors are used in some forms of renal impairment but they can also cause renal problems. So, how should the patient already on an ACE inhibitor with new ‘CKD' be managed?

41211353This scenario should prompt a search for previous results. A fall in GFR of less than 25% since the ACE inhibitor was started may simply reflect beneficial renal haemodynamic changes and the dose does not need modifying. Repeat within two weeks to confirm. If the fall has been 25% or more, look for hypotension, volume depletion or concurrent nephrotoxins.

Renal failure complicating ACE inhibitor therapy is almost always reversible. Stop the ACE inhibitor while you correct or remove these factors and then restart treatment once renal function has improved. But if no precipitating cause for the low eGFR is found, stop the ACE inhibitor or reduce the dose and add another antihypertensive if required.

Consider the possibility of high-grade renal artery stenosis if history or examination is suggestive, such as widespread atherosclerotic disease, long smoking history and so on.

After appropriate assessment and management of factors relevant to CKD, how often should eGFR be measured and what should prompt referral?

eGFR should be measured every six months and during intercurrent illness in patients such as this man with CKD stage 3.

Dr Berenice Lopez is specialist registrar in clinical biochemistry and metabolic medicine at North Bristol NHS Trust and a part-time GP

Competing interests: none declared

For more information on the use of lab tests in primary care go to BetterTesting.org.uk which has 120 clinical scenarios from general practice